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HIV functional impairment

Marjolein W J Wentink, Yvonne M Mueller, Virgil A S H Dalm, Gertjan J Driessen, P Martin van Hagen, Joris M van Montfrans, Mirjam van der Burg, Peter D Katsikis
Pathogenic gain-of-function mutations in the gene encoding phosphoinositide 3-kinase delta (PI3Kδ) cause activated PI3Kδ syndrome (APDS), a disease characterized by humoral immunodeficiency, lymphadenopathy, and an inability to control persistent viral infections including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Understanding the mechanisms leading to impaired immune response is important to optimally treat APDS patients. Immunosenescence of CD8+ T cells was suggested to contribute to APDS pathogenesis...
2018: Frontiers in Immunology
Ornella Sortino, Elizabeth Richards, Joana Dias, Edwin Leeansyah, Johan K Sandberg, Irini Sereti
: Chronic HIV-1 infection is associated with lower frequencies and functional impairment of mucosa-associated invariant T (MAIT) cells. We evaluated IL-7 treatment to restore MAIT cells in peripheral blood of chronically HIV-1-infected individuals on antiretroviral therapy. IL-7 led to increased relative and absolute levels of MAIT cells, and this expansion occurred primarily in the CD8 subset. These results suggest that IL-7 may represent a therapeutic intervention for the restoration of MAIT cells in chronic HIV-1 infection...
March 27, 2018: AIDS
Anas Z Abidin, Adora M DSouza, Mahesh B Nagarajan, Lu Wang, Xing Qiu, Giovanni Schifitto, Axel Wismüller
HIV is capable of invading the brain soon after seroconversion. This ultimately can lead to deficits in multiple cognitive domains commonly referred to as HIV-associated neurocognitive disorders (HAND). Clinical diagnosis of such deficits requires detailed neuropsychological assessment but clinical signs may be difficult to detect during asymptomatic injury of the central nervous system (CNS). Therefore neuroimaging biomarkers are of particular interest in HAND. In this study, we constructed brain connectivity profiles of 40 subjects (20 HIV positive subjects and 20 age-matched seronegative controls) using two different methods: a non-linear mutual connectivity analysis approach and a conventional method based on Pearson's correlation...
2018: NeuroImage: Clinical
Sérgio Monteiro de Almeida, Ana Paula de Pereira, Maria Lucia Alves Pedroso, Clea E Ribeiro, Indianara Rotta, Bin Tang, Anya Umlauf, Donald Franklin, Rowan G Saloner, Maria Geny Ribas Batista, Scott Letendre, Robert K Heaton, Ronald J Ellis, Mariana Cherner
Although cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections, research on neurocognitive effects is limited in the context of HIV/HCV co-infection. The aims of this study were to explore the interplay between HIV and HCV infections in the expression of neurocognitive impairment (NCI), and to examine the differences in test performance between HIV/HCV co-infected and HIV or HCV mono-infected patients. A total of 128 participants from Southern Brazil underwent a comprehensive neuropsychological (NP) battery comprising 18 tests...
March 7, 2018: Journal of Neurovirology
Savrina Manhas, Lina Ma, Vivien Measday
Nuclear pore complexes (NPCs) orchestrate cargo between the cytoplasm and nucleus and regulate chromatin organization. NPC proteins, or nucleoporins (Nups), are required for human immunodeficiency virus type 1 (HIV-1) gene expression and genomic integration of viral DNA. We utilize the Ty1 retrotransposon of Saccharomyces cerevisiae (S. cerevisiae) to study retroviral integration because retrotransposons are the progenitors of retroviruses and have conserved integrase (IN) enzymes. Ty1-IN targets Ty1 elements into the genome upstream of RNA polymerase (Pol) III transcribed genes such as transfer RNA (tRNA) genes...
March 5, 2018: Nucleic Acids Research
Trena Mukherjee, Rishanantini Sakthivel, Ho Yen Fong, Megan McStea, Meng Li Chong, Sharifah Faridah Omar, Ai Vyrn Chin, Shahrul Kamaruzzaman, Adeeba Kamarulzaman, Reena Rajasuriar, Lucette A Cysique
This study determines the optimal cut-off scores for the Montreal Cognitive Assessment (MoCA) to detect HIV-associated neurocognitive disorders (HAND) in a multi-ethnic Malaysian HIV-positive cohort by developing demographically corrected normative standards among 283 HIV-negative community-based controls with overlapping demographic characteristics. The norms (corrected for age, sex, education, ethnicity) were applied to 342 HIV-positive virally suppressed individuals on cART. Impairment rates were classified using the Global Deficit Score (GDS ≥ ...
March 5, 2018: AIDS and Behavior
Norma Kabuba, J Anitha Menon, Donald R Franklin, Stian Lydersen, Robert K Heaton, Knut A Hestad
OBJECTIVE: Older age and lower education levels are known to be associated with worse neurocognitive (NC) performance in healthy adults, and individuals with HIV infection may experience accelerated brain/cognition aging. However, higher education may possibly protect against HIV-associated neurocognitive disorders (HAND). The aim of the current cross-sectional study was to assess the effect of age and education in an HIV-1 clade C infected adult population in urban Zambia. METHOD: Demographically corrected Zambian norms on a neuropsychological (NP) test battery were used to correct for normal age and education effects...
March 5, 2018: Neuropsychology
Anthony A Duplanty, Robert W Siggins, Timothy Allerton, Liz Simon, Patricia E Molina
Work from our group demonstrated that chronic binge alcohol (CBA)-induces mitochondrial gene dysregulation at end-stage disease of simian immunodeficiency virus (SIV) infection in antiretroviral therapy (ART) naïve rhesus macaques. Alterations in gene expression can disrupt mitochondrial homeostasis and in turn contribute to the risk of metabolic comorbidities characterized by loss of skeletal muscle (SKM) functional mass that are associated with CBA, human immunodeficiency virus (HIV) infection, and prolonged ART...
March 2018: Physiological Reports
Jens D Lundgren, Alvaro H Borges, James D Neaton
PURPOSE OF REVIEW: Optimal control of HIV can be achieved by early diagnosis followed by the initiation of antiretroviral therapy (ART). Two large randomised trials (TEMPRANO and START) have recently been published documenting the clinical benefits to HIV-positive adults of early ART initiation. Main findings are reviewed with a focus on serious non-AIDS (SNA) conditions. RECENT FINDINGS: Data from the two trials demonstrated that initiating ART early in the course of HIV infection resulted in marked reductions in the risk of opportunistic diseases and invasive bacterial infections...
March 5, 2018: Current HIV/AIDS Reports
Miriam Chernoff, Konstantia Nadia Angelidou, Paige L Williams, Pim Brouwers, Meredith Warshaw, Sharon Nachman
Brief psychiatric assessment tools are needed for evaluating children affected by HIV for emotional and behavioral problems. We compared a self-administered symptom rating scale (CASI-4R) to a semi-structured diagnostic interview (DICA-P) in 136 U.S. children affected by HIV. Agreement and performance measures for the two instruments were computed for attention deficit hyperactivity disorder, depression, anxiety, and disruptive behavior. Correlations and regression analyses were conducted to compare the two instruments, and to evaluate their associations with social, academic, and global function...
February 19, 2018: Journal of Clinical Psychology in Medical Settings
Anika Hain, Melanie Krämer, René M Linka, Saeideh Nakhaei-Rad, Mohammad Reza Ahmadian, Dieter Häussinger, Arndt Borkhardt, Carsten Münk
Successful replication of Human immunodeficiency virus (HIV)-1 depends on the expression of various cellular host factors, such as the interleukin-2 inducible T-cell kinase (ITK), a member of the protein family of TEC-tyrosine kinases. ITK is selectively expressed in T-cells and coordinates signaling pathways downstream of the T-cell receptor and chemokine receptors, including PLC-1 activation, Ca 2+ -release, transcription factor mobilization, and actin rearrangements. The exact role of ITK during HIV-1 infection is still unknown...
February 16, 2018: Scientific Reports
M Mohamed, P B Barker, R L Skolasky, N Sacktor
BACKGROUND AND PURPOSE: Validated neuroimaging markers of HIV-associated neurocognitive disorder in patients on antiretroviral therapy are urgently needed for clinical trials. The purpose of this study was to explore the relationship between cognitive impairment and brain metabolism in older subjects with HIV infection. It was hypothesized that MR spectroscopy measurements related to neuronal health and function (particularly N -acetylaspartate and glutamate) would be lower in HIV-positive subjects with worse cognitive performance...
February 15, 2018: AJNR. American Journal of Neuroradiology
Padraig McGettrick, Elena Alvarez Barco, Patrick W G Mallon
The population of people living with HIV (PLWH) is growing older with an estimated 4 million over the age of 50 years, a figure which has doubled since the introduction of effective antiretroviral therapy (ART) and which is increasing globally. Despite effective ART, PLWH still experience excess morbidity and mortality compared to the general population with increased prevalence of age-related, non-AIDS illnesses (NAI) such as cardiovascular disease, malignancies, cognitive impairment and reduced bone mineral density, which impact disability and everyday functioning...
February 14, 2018: Healthcare (Basel, Switzerland)
Uraina S Clark, Miguel Arce Rentería, Rachal R Hegde, Susan Morgello
There is burgeoning evidence that, among HIV+ adults, exposure to high levels of early life stress (ELS) is associated with increased cognitive impairment as well as brain volume abnormalities and elevated neuropsychiatric symptoms. Currently, we have a limited understanding of the degree to which cognitive difficulties observed in HIV+ High-ELS samples reflect underlying neural abnormalities rather than increases in neuropsychiatric symptoms. Here, we utilized a behavioral marker of cognitive function, reaction time intra-individual variability (RT-IIV), which is sensitive to both brain volume reductions and neuropsychiatric symptoms, to elucidate the unique contributions of brain volume abnormalities and neuropsychiatric symptoms to cognitive difficulties in HIV+ High-ELS adults...
2018: Frontiers in Behavioral Neuroscience
Borja Mora-Peris, George Bouliotis, Kulasegaram Ranjababu, Amanda Clarke, Frank A Post, Mark Nelson, Laura Burgess, Juan Tiraboschi, Saye Khoo, Steve Taylor, Deborah Ashby, Alan Winston
BACKGROUND: Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits. METHODS: Therapy naïve, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1:1 basis to standard ART (Arm1; tenofovir-emtricitabine plus atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine plus darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function (CF) tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy...
February 12, 2018: AIDS
Richard A Elion, Keri N Althoff, Jinbing Zhang, Richard D Moore, Stephen J Gange, Mari M Kitahata, Heidi M Crane, Daniel R Drozd, James H Stein, Marina B Klein, Joseph J Eron, Michael J Silverberg, William C Mathews, Amy C Justice, Timothy R Sterling, Charles S Rabkin, Angel M Mayor, Daniel B Klein, Michael A Horberg, Ronald J Bosch, Oghenowede Eyawo, Frank J Palella
BACKGROUND: There is persistent confusion as to whether abacavir (ABC) increases the risk for myocardial infarction (MI), and whether such risk differs by Type 1 (T1MI) or 2 (T2MI) MI in adults with HIV. METHODS: Incident MIs in NA-ACCORD participants were identified from 2001 to 2013. Discrete time marginal structural models addressed channeling biases and time-dependent confounding to estimate crude (HR) and adjusted hazard ratios (aHR) and 95% confidence intervals; analyses were performed for T1MI and T2MI separately...
February 6, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Martha Martínez-Banfi, Jorge I Vélez, M Victoria Perea, Ricardo García, Pedro J Puentes-Rozo, Moises Mebarak Chams, Valentina Ladera
Human immunodeficiency virus (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) lead to neurocognitive disorders; however, there is still much knowledge to be gained regarding HIV-associated neurocognitive disorders. The purpose of this study was to assess the cognitive performance, instrumental activities of daily living, depression, and anxiety in patients with asymptomatic HIV-1 infections compared with seronegative participants without neurocognitive impairment. We studied a sample consisted of 60 patients with asymptomatic HIV-1 infections and 60 seronegative participants without neurocognitive impairment from the city of Barranquilla, Colombia, with a mean age of 36...
February 7, 2018: AIDS Care
L Shang, A J Smith, L Duan, K E Perkey, S Wietgrefe, M Zupancic, P J Southern, R P Johnson, J V Carlis, A T Haase
To identify mechanisms by which HIV-1 might penetrate the epithelial barrier during sexual transmission to women and vaccine-associated protection against entry, we characterized early epithelial responses to vaginal inoculation of SIVmac251 in naïve or SIVmac239Δnef-vaccinated rhesus macaques. Vaginal inoculation induced an early stress response in the cervicovaginal epithelium, which was associated with impaired epithelial integrity, damaged barrier function, and virus and bacterial translocation. In vaccinated animals, early stress responses were suppressed, and the maintenance of epithelial barrier integrity correlated with prevention of virus entry...
February 1, 2018: Journal of Infectious Diseases
Tracy Evans-Gilbert, Kazie Kasimbie, Gail Reid, Shelly Ann Williams
Background Psychosocial factors interact with adolescent development and affect the ability of HIV-infected adolescents to cope with and adhere to treatment. Aim To evaluate psychosocial outcomes in perinatally HIV-infected adolescents (PHIVAs) in Western Jamaica after psychosocial intervention. Methods The Bright Futures Paediatric Symptom Checklist (BF-PSC) was used for psychological screening of PHIVAs in Western Jamaica. Referred patients were evaluated using the Youth version of the Columbia Impairment Scale (CIS)...
February 5, 2018: Paediatrics and International Child Health
M J Álvarez-Ossorio, R Sarmento E Castro, R Granados, J Macías, L E Morano-Amado, M J Ríos, D Merino, E N Álvarez, A Collado, M Pérez-Pérez, F Téllez, J M Martín, J Méndez, J A Pineda, K Neukam
Little data are available on renal toxicity exerted by direct-acting antivirals (DAAs) in real life. The aim of this study was to assess the impact of direct-acting antivirals against hepatitis C virus infection currently used in Spain and Portugal on the estimated glomerular filtration rate (eGFR) in clinical practise. From an international, prospective multicohort study, patients treated with DAAs for at least 12 weeks and with eGFR ≥30 mL/min per 1.73 m2 at baseline were selected. eGFR was determined using the CKD-EPI formula...
January 28, 2018: Journal of Viral Hepatitis
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